Sodium butyrate-activated TRAF6-TXNIP pathway affects A549 cells proliferation and migration.
Xiaoqiang XiaoYanxuan XuHaoyu ChenPublished in: Cancer medicine (2019)
TNF receptor-associated factor 6 (TRAF6) promotes the development of human lung cancer through bridging RAS and NF-kB pathways; on the other hand, thioredoxin-interacting protein (TXNIP) suppresses the growth of tumors. However, the crosstalk between TRAF6 and TXNIP in non-small cell lung cancer (NSCLC) is currently unclear. Here, we found that TXNIP expression induced by sodium butyrate (NaBu) was TRAF6-dependent. Moreover, TXNIP interacted with TRAF6 via its PPxY motif. Polyubiquitylation analysis with wild-type or mutant (Cysteine70 to Alanine) of TRAF6 further showed TRAF6 ubiquitylated TXNIP. NaBu reinforced the interaction of TRAF6/TXNIP as well as TXNIP' polyubiquitylation. Moreover, treated with NaBu, the A549 cells with TRAF6/TXNIP double knockdown showed an enhanced protein expression of E-cadherin comparing to cells with single gene or negative knockdown. The experimental results of transwell and nude mice xenograft showed that knocking down both TRAF6 and TXNIP in A549 cells affected its migration and proliferation compared to that of single knockdown or negative control cells. On the other hand, TXNIP localization was different depending on the cell types and fused-tag (eg, FLAG or GFP). Our results revealed TRAF6 regulated the expression and polyubiquitylation of TXNIP in a NaBu-dependent manner, alleviating tumorigenesis of TRAF6.
Keyphrases
- nlrp inflammasome
- induced apoptosis
- cell cycle arrest
- signaling pathway
- wild type
- endoplasmic reticulum stress
- oxidative stress
- small cell lung cancer
- type diabetes
- rheumatoid arthritis
- single cell
- metabolic syndrome
- cell death
- dna methylation
- gene expression
- inflammatory response
- skeletal muscle
- transcription factor
- binding protein
- genome wide
- adipose tissue
- copy number
- advanced non small cell lung cancer
- insulin resistance
- single molecule
- protein kinase